acetylstrophanthidin and Coronary-Disease

The effect of acetyl-strophanthidin, a rapidly acting digitalis-like drug, was measured on peak flow velocity, stroke distance (an index of stroke volume) and minute distance (an index of cardiac output), determined by Doppler echocardiography in 21 subjects with a wide range of left ventricular ejection fractions (12 to 89%, average 47%). For the total study group, peak flow velocity increased from 99 +/- 10 to 110 +/- 13 cm/s (p less than 0.01), and stroke distance increased from 15.1 +/- 3.2 to 16.8 +/- 3.1 cm (p less than 0.01). Minute distance remained unchanged: 1,093 +/- 168 cm before and 1,129 +/- 187 cm after acetyl-strophanthidin (difference not significant). Improvement in Doppler parameters of forward blood flow was significantly (p less than 0.001) greater in subjects with left ventricular ejection fractions less than 60% (+17% for peak flow velocity, +22% for stroke distance and +15% for minute distance) than those with left ventricular ejection fractions greater than or equal to 60% (+4% for peak flow velocity, +2% for stroke distance and -8% for minute distance). These data suggest that Doppler echocardiography is a useful method to assess the efficacy of acute digitalis administration in improving forward blood flow.

Topics: Blood Flow Velocity; Cardiomyopathy, Dilated; Cardiotonic Agents; Coronary Disease; Digitalis Glycosides; Echocardiography, Doppler; Female; Hemodynamics; Humans; Male; Middle Aged; Strophanthidin

The aim of this study was to determine if "ischemia" and/or reperfusion potentiate digitalis toxicity through effects on oscillatory afterpotentials. Isolated canine Purkinje tissue-papillary muscle preparations were studied using standard microelectrode techniques. Tissues were superfused for 10 min with an "ischemic" solution that mimicked hypoxia, acidosis, elevated lactate, zero substrate and normo- or hyperkalemia. Reperfusion with "normal" Tyrode's solution was then reinstated for 60 min. Next, subthreshold oscillatory after potentials were induced with acetylstrophanthidin (ACS) and the protocol was repeated with ACS in all solutions. Without ACS, ischemic conditions with 4 mM KCl caused depolarization of Purkinje and muscle tissues. Reperfusion resulted in hyperpolarization of Purkinje tissue followed by mild depolarization, and then recovery. Purkinje tissue exposed to ischemic conditions with hyperkalemia responded similarly, except that hyperpolarization upon reperfusion was absent. In the presence of ACS, ischemic conditions with 4 mM KCl abolished oscillatory afterpotentials and caused marked depolarization of Purkinje tissue. Reperfusion decreased the coupling intervals and increased the amplitude of oscillatory afterpotentials relative to pre-ischemic levels, and frequently elicited arrhythmic activity. Arrhythmias ceased and tissues recovered by 60 min of reperfusion. Ischemic conditions incorporating hyperkalemia also abolished ACS-induced oscillatory afterpotentials and delayed their reappearance upon reperfusion. All other reperfusion responses were similar. This study demonstrates that "ischemic" suppresses oscillatory afterpotential-mediated effects of digitalis in canine Purkinje tissue, whereas reperfusion potentiates oscillatory afterpotential-induced arrhythmias.

Topics: Action Potentials; Animals; Arrhythmias, Cardiac; Calcium; Coronary Disease; Dogs; In Vitro Techniques; Male; Perfusion; Potassium; Purkinje Fibers; Sodium-Potassium-Exchanging ATPase; Strophanthidin

The purpose of this study was to determine if sensitization of cardiac receptors with acetylstrophanthidin augments the inhibition of renal nerve activity resulting from expansion of the blood volume or from coronary artery occlusion. Ten chloralose-anesthetized dogs with sinoaortic baroreceptor denervation were subjected to volume expansion with dextran in saline. Under control conditions, volume expansion resulted in decreases in renal nerve activity (% or control) that were inversely related to left atrial pressure (-13.0%/mmHg left atrial pressure). After intracoronary acetylstrophanthidin, volume expansion resulted in a significantly greater suppression of renal nerve activity (-20.6%/mmHg). Occlusion of the circumflex coronary artery in 19 dogs with carotid baroreceptor denervation resulted in a 29 +/- 5% (SE) reduction in renal nerve activity. After intracoronary acetylstrophanthidin, circumflex occlusion resulted in a significantly greater decrease in renal nerve activity (45 +/- 4%). Vagotomy abolished the decreases in renal nerve activity, which resulted from volume expansion and from circumflex coronary occlusion. These data show that volume expansion and coronary occlusion reflexly decrease renal nerve activity via cardiac afferent vagal endings. These reflex inhibitory influences are augmented after intracoronary acetylstrophanthidin. The results are consistent with the view that intracoronary acetylstrophanthidin sensitizes cardiac afferent vagal endings.

Topics: Afferent Pathways; Animals; Blood Volume; Coronary Disease; Dogs; Heart; Hemodynamics; Kidney; Mechanoreceptors; Reflex; Strophanthidin; Vagus Nerve